Observations  After a washout phase of 2 weeks, patients were randomized to receive 0.005% calcipotriol ointment twice daily, placebo ointment once daily, or 0.3% tacrolimus ointment once daily. One psoriatic plaque was treated with a surface area of 40 to 200 cm². Efficacy was estimated using the local psoriasis severity index. The reduction in the local psoriasis severity index score after 6 weeks was 62.5% in the calcipotriol group, 33.3% in the tacrolimus group, and 42.9% in the placebo group.

Conclusions  There was no statistically significant difference between the efficacy of tacrolimus and placebo ointment (P=.77). Calcipotriol ointment, applied twice daily, had a better effect than tacrolimus ointment and placebo ointment once daily.

For dermatology, a topical formulation of these macrolactam-type cyclic immunosuppressive drugs is an interesting pharmaceutical option. The first studies with topical tacrolimus were performed in 1987.⁵ Topical tacrolimus was not effective, either in psoriasis or in allergic or atopic eczema.^6-7 The ascomycine derivative ASM 281-240⁸ has also been used topically under occlusion in psoriasis, with promising results. However, a confirmatory study has not been published. Topical tacrolimus was studied in atopic eczema and contact allergy, where it has been successful.^9-12 Topical tacrolimus also has been studied under occlusion on descaled psoriatic skin in microplaques, and in this model topical tacrolimus showed efficacy.¹³

We have studied the possible efficacy of topical tacrolimus in psoriasis in a 3-armed study for 6 weeks.

PATIENTS AND STUDY DESIGN

RESULTS

COMMENT

Tacrolimus is a 822.05-d molecule that appears to be effective in atopic eczema but not in psoriasis when used as a topical drug. This result might be explained by assuming that the molecular weight prevents penetration into psoriatic skin. Systemic tacrolimus is effective in treating psoriasis. Because of a probable skin barrier defect, molecules with a molecular weight between 800 and 1200 d can penetrate the skin and thus are effective in treating atopic eczema. Furthermore, it is striking that all cyclic topical immunosuppressive drugs have a molecular weight greater than 800 d. Both corticosteroids (mean molecular weight around 450 d) and calcipotriol (molecular weight, 413 d), the 2 drugs that have been proven to be effective in psoriasis, have molecular weights less than 500 d. Until now the only exceptions to the 500-d barrier hypothesis are the studies with oxyclosporine (SDZ 281-240) by Rappersberger et al⁸ and the study with topical tacrolimus by Remitz et al,¹³ in which these macrolactams with a molecular weight slightly greater than 800 d were found to have an effect on psoriasis. The efficacy might be related to the occlusive effect of the Finn chambers used in these studies. If a topical formulation could be designed that will enhance penetration in psoriatic skin by first disrupting the skin barrier function, macrolactam-type cyclic immunosuppressive drugs probably would be effective in a topical formulation. Another option is the development of cyclic immunosuppressant drugs with a lower molecular weight.

This study was sponsored by Fujisawa GmbH, Munich, Germany.

Reprints: I. M. Zonneveld, MD, Department of Dermatology, Academisch Medisch Centrum, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, the Netherlands.